Test Detail

Progressive leukodystrophy characterised by degeneration of the white matter with accumulation of Rosenthal fibres. In humans it is caused by gain-of-function mutations in the GFAP gene, which encodes glial fibrillary acidic protein. In the dog, an equivalent picture has been molecularly confirmed in one Labrador Retriever, with a GFAP variant orthologous to the human hotspot and a dominant pattern; the condition is juvenile-onset, progressive and fatal.

Limited data: a single molecularly confirmed case in a Labrador Retriever. The disease is considered very rare in the canine species and there are no reliable population frequencies.

- In the face of progressive neurological signs in young animals, refer to neurology and MRI before any breeding decision\n- Do not mate animals with a history of similar conditions in the line\n- In the face of a confirmed case, do not repeat the parental mating\n- Breeding advice is cautious because of the uncertainty about canine inheritance

Broad differential diagnosis with other canine leukodystrophies (greyhound leukodystrophy, Rottweiler multifocal leukoencephalopathy), degenerative myelopathies, meningoencephalitis and toxic-metabolic processes. MRI shows white matter involvement; definitive diagnosis requires histopathology (GFAP-positive Rosenthal fibres) and GFAP study. As it is a dominant variant, breeding advice must be cautious and consider that an affected parent can transmit the allele to 50 % of the offspring.

1. Van Poucke M et al. (2016) A canine orthologue of the human GFAP c.716G>A (p.Arg239His) variant causes Alexander disease in a Labrador retriever. Eur J Hum Genet 24:852-6. PMID: 26486469
2. OMIA:001208-9615. Alexander disease in Canis lupus familiaris. https://omia.org/OMIA001208/9615/